8-10239916-A-T

Variant names:

• chr8-10239916-A-T
• rs2975721
• NM_012331.5:c.212-5188A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012331.5(MSRA):​c.212-5188A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,006 control chromosomes in the GnomAD database, including 5,656 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5656 hom., cov: 33)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547
• Publications: 2 publications found

Genes affected

MSRA (HGNC:7377): (methionine sulfoxide reductase A) This gene encodes a ubiquitous and highly conserved protein that carries out the enzymatic reduction of methionine sulfoxide to methionine. Human and animal studies have shown the highest levels of expression in kidney and nervous tissue. The protein functions in the repair of oxidatively damaged proteins to restore biological activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5	c.212-5188A>T		intron_variant	Intron 2 of 5	ENST00000317173.9	NP_036463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSRA	ENST00000317173.9	c.212-5188A>T		intron_variant	Intron 2 of 5	1	NM_012331.5	ENSP00000313921.4

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38086 AN: 151888 Hom.: 5636 Cov.: 33

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.242

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.251 AC: 38156 AN: 152006 Hom.: 5656 Cov.: 33 AF XY: 0.247 AC XY: 18365 AN XY: 74298

African (AFR) AF: 0.400 AC: 16550 AN: 41408

American (AMR) AF: 0.192 AC: 2930 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 554 AN: 3464

East Asian (EAS) AF: 0.342 AC: 1763 AN: 5158

South Asian (SAS) AF: 0.343 AC: 1657 AN: 4830

European-Finnish (FIN) AF: 0.128 AC: 1352 AN: 10562

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12596 AN: 67990

Other (OTH) AF: 0.244 AC: 514 AN: 2108

Alfa AF: 0.219 Hom.: 520

Bravo AF: 0.265

Asia WGS AF: 0.364 AC: 1263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.61
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2975721; hg19: chr8-10097426;